The objective of the project is to study a syndrome of spontaneous onset diabetes in rats, which appears to be the animal model most closely resembling human insulin dependent diabetes. Preliminary studies indicate autoimmunity is very likely to play a role in pathogenesis and appears to cause destruction of transplanted pancreatic islets even if rejection is prevented. Specific aims of the grant include study and manipulation of the genetic setting of the disease and attempts to confirm the autoimmune nature by transferring the condition to non diabetic rats by means of "immune" lymphocytes. Diabetic and prediabetic rats hve been found to have some characteristics of immune deficiency. We will attempt to define the responsible factors (e.g. abnormal T cell function) in the immunodeficiency and to determine whether it is causally related to the diabetes. We will also investigate possible reasons for our observation that transplantation of bone marrow from normal donors to members of the diabetes prone stock decreases the incidence of diabetes.